A discovery that two commonly used food additives are estrogenic has led scientists to suspect that many ingredients added to the food supply may be capable of altering hormones.

More than 3,000 preservatives, flavorings, colors and other ingredients are added to food in the United States, and none of them are required to undergo testing for estrogenic activity, according to the Food and Drug Administration.

“We need to be mindful of these food additives because they could be adding to the total effect of other estrogen mimicking compounds we're coming into contact with,” said Clair Hicks, a professor of food science at the University of Kentucky and spokesperson for the Institute of Food Technologists, a nonprofit scientific group.

“The benefits of using these additives in food need to be weighed against the risks they present,” Hicks said.

In a study published in December, Italian researchers screened 1,500 food additives using computer-modeling software, a much faster and cheaper approach than testing lab rats.

The researchers first used modeling to identify 13 molecules that could hypothetically bind with an estrogen receptor, a group of molecules activated by the hormone. Like a clenched fist that fits into the palm of a hand, potentially estrogenic molecules will “fit” inside the receptor, indicating they could interact and alter hormones.

Then, the researchers exposed cells to the 13 food additives, which confirmed that two have estrogen-mimicking properties. Known as “xenoestrogens,” these substances have been linked to reproductive problems in animals and perhaps humans.

The first food additive, propyl gallate, is a preservative used to prevent fats and oils from spoiling that can be found in a range of foods including baked goods, shortening, dried meats, candy, fresh pork sausage, mayonnaise and dried milk.

The second additive, 4-hexyl resorcinol, is used to prevent shrimp, lobsters, and other shellfish from discoloring.

“Some caution should be issued for the use of these two additives,” said Pietro Cozzini, one of the researchers who conducted the study and a chemistry professor at the University of Parma in Italy.

He added that further tests on rats are necessary to determine whether these additives could harm humans.

Paul Foster, whose research focuses on the potential human health effects of endocrine disruptors, agreed. He said there is a big difference between adding estrogenic molecules to cells in a culture dish and actually seeing what happens when that dose is administered to an animal.

“There are a lot of compounds that give quite strong responses in a culture dish that really don’t produce any effects on lab rats,” said Foster, who is deputy director of the National Toxicology Program's Center for the Evaluation of Risks to Human Reproduction, which is part of the National Institutes of Health.

The major concern, Foster said, is what happens when people are exposed to mixtures of these estrogenic compounds.

“There are examples where you can take dose levels of compounds on their own that won’t produce an effect, but when you put these compounds together, you may get something different,” he said.

However, Foster said people should keep in mind that they already ingest significant numbers of fairly potent estrogens in their diets by consuming foods like tofu and milk, so findings like these shouldn’t necessarily scare people until more research has been conducted.

“It’s clear that humans are exposed to a mixture of these estrogenic compounds,” Foster said. “But you have to try to balance out what might already be present in your diet or your lifestyle with these things that might be coming from some other sources,” such as food additives.

Systems like the one used by the Italian researchers are useful for screening potentially estrogenic additives, Foster said, adding that it’s a “good first step” towards identifying these compounds.

Of the estimated 3,000 additives used in the United States to preserve foods or improve their taste and appearance, only about 2,000 have detailed toxicological information available, according to the FDA.

"Our results are part of a bigger, more important problem, which is that there could be other additives used in foods that could have estrogenic activity," Cozzini said.

Globally, the market for additives is expected to reach more than $33 billion by 2012. There are five main reasons that companies add compounds to food: to emulsify, to preserve, to add nutritional content, to add flavor or color and to balance alkalinity and acids.

"With some 3,000 compounds being used in food formulations there may be other additives with estrogenic properties that come to light with these types of studies," Hicks said.

Using the traditional animal testing system, “it would be impossible to test all of the additives in a short time,” Cozzini said. “Every day we discover new molecules, and we must continue to identify new ways to study them.”

Propyl gallate is considered “Generally Recognized As Safe” (GRAS) by the FDA, a title given to food additives that don’t require approval because they have a proven track record based on either a history of use before 1958 or on published scientific evidence. Examples of other GRAS substances include salt, sugar, spices and vitamins.

The other estrogenic one, 4-hexyl resorcinol, which is used on raw shelled seafood to inhibit melanosis, or black spots, was petitioned in 1990 for GRAS status. Its status is still pending, according to Michael Herndon, an FDA press officer.

The FDA’s lack of testing for estrogenic compounds doesn’t stop at additives. In 2008, an independent advisory board said the FDA ignored critical evidence concerning another estrogenic compound, bisphenol A, a plasticizing chemical found in polycarbonate baby bottles and the linings of metal foods cans.

“What we’ve seen with the FDA’s handling of BPA is that it’s had its head in the sand,” said Renee Sharp, director of the Environmental Working Group’s California office. “If you look at its assessments, what you see is that it has consistently ignored independent science and consistently used outdated methods in its assessments.”

As concern about the cumulative impacts of these chemicals grows among the scientific community, some studies are suggesting that the effects of these compounds could extend to future generations.

For example, investigators at the National Institute of Environmental Health Sciences have found that adverse effects can be seen in both the granddaughters and grandsons of mice who were developmentally exposed to diethylstilbestrol (DES), a synthetic form of estrogen that caused reproductive problems in pregnant women and their fetuses. While DES was taken off the market in 1971, there are many other compounds that have similar, estrogenic effects.

“This study is the flagship of estrogen mimickers and why we worry about them,” said Shanna Swan, director of the University of Rochester's Center for Reproductive Epidemiology and a leading expert on reproductive effects of environmental exposures. “The fact that these chemicals can effect future generations has been a huge lesson for the science community.”

Other research has found that low doses of these chemicals can cause significant changes in those exposed to them and their developing offspring. One recent study published in Environmental Health Perspectives found that when rats are exposed to low levels of BPA during lactation, their offspring had an increased chance of breast cancer.

As the evidence that synthetic estrogens may pose a health risk mounts, researchers are uncovering these compounds in new places.

Earlier this month, researchers in Germany found traces of an unknown estrogenic substance leaching into mineral water stored in polyethylene terephthalate (PET) bottles, a commonly used plastic for storing foods and beverages.

The study is the first to find that these containers are leaching synthetic estrogens.

“We already knew that BPA was leaching from polycarbonate baby bottles, so we decided to test bottles of mineral water to see if there was any estrogenic activity,” said Martin Wagner, a PhD student in aquatic toxicology at Johann Wolfgang Goethe University in Frankfurt.

The scientists tested 20 brands of mineral water and found that 60 percent of the samples tested positive, with estrogenic activity in plastic bottles appearing twice as high as compared to activity in water from glass bottles.

In addition, the researchers found that mud snails placed inside the bottles filled with fresh water experienced reproduction rates double of control snails, which suggests that substances from the packaging, and not the water itself, caused the reproductive change.

“The results show that these leached chemicals are important enough to change reproduction in only eight weeks,” Martin said.

Further testing is needed to identify the source of the estrogenic activity, but Wagner said the study’s significance is that it shows people are exposed to more environmental endocrine disruptors than what was previously thought.

“We’re dealing with this chemical mixture, a cocktail effect, and I would say that if you look at a single compound then you might underestimate the exposure to these environmental estrogens,” he said.

Ralph Vasami, executive director of a plastics industry group, the PET Resin Association, said ongoing research on the safety of PET for the past three decades has revealed no safety issues or reasons for concern.

"PET has been proven through considerable research to be a safe packaging material for water and other food and beverage items,” he said. “The PET industry stands on its record of safety and reliability as a packaging material.”

Swan said that the studies reinforce the need for precautionary action when dealing with these types of chemicals, such as avoiding plastic products whenever possible to decrease exposure.
“If you’re taking several hits of something, even if it’s safe at a low dose, it’s going to add up,” Swan said.

This article originally ran at Environmental Health News, a news source published by Environmental Health Sciences, a nonprofit media company.

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